A great variety of skin manifestations and the frequent occurrence of cold sensitivity, vascular symptoms with peripheral painful ulcerations, headache of migraine type, and muscle and joint symptoms are described in a series of 12 patients with an overlap syndrome compatible with mixed connective tissue disease (MCTD). The patients have been followed up for an average of 7 years. The peripheral symptoms on the extremities in particular were exacerbated by exposure to cold and caused much inconvenience and early disability for the patients. In addition to the symptoms generally connected with MCTD, some of the patients presented signs of other diseases of autoimmune type as well. For instance 2 of the patients presented autoimmune thyroiditis and one patient developed myasthenia gravis and cold agglutinin syndrome.